Organs are transplanted clinically to rectify an irreversible function
al deficit but, unless donor and recipient are genetically identical,
graft antigens will trigger a rejection response by the recipient. In
the early part of this century, experiments on transplantation of tumo
urs showed that there were strict limitations on the ability of tumour
grafts to survive. These 'laws of transplantation' were confirmed by
the elegant work of Sir Peter Medawar and colleagues who also showed t
hat rejection is a systemic process governed by lymphocytes. The study
of skin graft rejection in mice led to the discovery of the major his
tocompatibility complex (MHC) antigens, the function of which is to bi
nd processed antigens and present them to T lymphocytes. T lymphocytes
are pivotal in transplant rejection. The sensitization phase of rejec
tion is due mainly to passenger leucocytes in the graft being recognis
ed as foreign by the recipient's CD4(+) T cells. The effector phase of
rejection involves these activated recipient T cells entering the gra
ft and locally producing cytokines. The rate of rejection depends on t
he relative contribution of the underlying immunological effector mech
anisms. Our understanding of the role of T cells in transplant rejecti
on has contributed much to knowledge on T cell physiology and function
. The need to prevent rejection has also led to the development and us
e of new immunomodulating agents, approaches which have implications i
n the treatment of many other immunological disorders.